In this interdisciplinary clinical center proposal we are combining the clinical and research expertise of 26 persons. All have an appointment in the Department of Neurology at Johns Hopkins, but their expertise also includes the areas of clinical neurology, veterinary medicine, neuropathology, neuroimmunology, neurochemistry, and basic neurobiology. We are focusing on the following disease processes for which we have active basic and clinical research pzograms: 1. MS and Related Diseases; 2. Diseases that Affect Neurons: Studies of Normal and Abnormal Neurons; 3. Diseases of Motor Neurons; 4. Diseases of Peripheral Nerve; and 5. Myasthenia Gravis. Even though these diseases have different clinical manifestations, the approaches to understanding the underlying processes may be quite similar. For example, in each disease there is selective cellular dysfunction or cell loss. Studies of selective vulnerability of neural cells to viruses, of antigenic markers, of analysis of axonal flow in disease and repair, and of abnormalities of neural transmission may prove relevant to any or all of the disease mechanisms. It is the goal of this center grant to provide central support for ongoing basic studies, for following new leads, and for extending the results clinically to diagnosis and treatment. Previous interdisciplinary research produced clinical advances including a test for disease activity in multiple sclerosis, delineation of antigenic shift of virus as a mechanism of relapsing disease of the nervous system, the role of antibodies to the acetylcholine receptor in myasthenia gravis, and the development of models of motor neuron disease. In this proposal, we will continue to study neurological disease by: (a) understanding the basic mechanisms; (b) characterization of animal models of human disease; (c) development of methods for detecting disease and monitoring its activity; and (d) establishing logical approaches to therapy.